CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen.
CpG DNA is a potent enhancer of specific immunity in mice immunized with recombinant hepatitis B surface antigen.
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DOI：
10.4049/jimmunol.160.2.870
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发表时间：
1998-01
影响因子：
4.4
通讯作者：
H. Davis;Risini Weeranta;T. Waldschmidt;L. Tygrett;J. Schorr;A. Krieg
中科院分区：
文献类型：
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作者：
H. Davis;Risini Weeranta;T. Waldschmidt;L. Tygrett;J. Schorr;A. Krieg
细菌 DNA 或合成寡脱氧核苷酸 (ODN) 中的未甲基化 CpG 二核苷酸可在体内和体外引起 B 细胞增殖和 Ig 分泌、单核细胞细胞因子分泌、NK 细胞裂解活性激活和 IFN-γ 分泌。 CpG ODN 的有效免疫激活表明其可能有助于增强疫苗的免疫反应。用重组乙型肝炎病毒表面抗原和 CpG ODN 作为免疫增强剂免疫的小鼠，其抗 HBsAg 的抗体（抗 HBs）滴度比用 HBsAg 和标准佐剂氢氧化铝（明矾）免疫的小鼠高出五倍。用 HBsAg 和 CpG ODN 加明矾免疫的小鼠中的抗体滴度比单独用明矾免疫的小鼠中的滴度高 35 倍，表明 CpG ODN 和明矾之间存在很强的协同相互作用。没有CpG基序的ODN在本文使用的剂量下几乎没有或没有免疫增强活性。明矾诱导 Th2 体液反应（主要是 IgG1），但不诱导 CTL。相比之下，即使与明矾混合，CpG ODN 也会对主要是 IgG2a Abs 和 CTL 产生强烈的 Thl 反应。确定 CpG 免疫增强作用可能机制的体外研究表明，CpG ODN 诱导 Ag 呈递细胞上共刺激分子的表达，并在适当的细胞因子环境中驱动 B 细胞同种型转换。这些研究表明，CpG ODN 是用于疫苗接种应用的有前途的新型免疫增强剂。
Unmethylated CpG dinucleotides in bacterial DNA or synthetic oligodeoxynucleotides (ODN) cause B cell proliferation and Ig secretion, monocyte cytokine secretion, and activation of NK cell lytic activity and IFN-gamma secretion in vivo and in vitro. The potent immune activation by CpG ODN suggests possible utility for enhancing immune responses to vaccines. Mice immunized with recombinant hepatitis B virus surface Ag and a CpG ODN as an immune enhancer have titers of Abs against HBsAg (anti-HBs) that are five times higher than those of mice immunized with HBsAg and the standard adjuvant, aluminum hydroxide (alum). Ab titers in mice immunized with HBsAg and both CpG ODN plus alum were 35 times higher than the titers in mice immunized with alum alone, indicating a strong synergistic interaction between the CpG ODN and alum. ODN without CpG motifs had little or no immune-enhancing activity at the doses used herein. Alum induces a Th2 humoral response (mostly IgG1) and no CTL. In contrast, CpG ODN gives a strong Thl response with predominantly IgG2a Abs and CTL, even when mixed with alum. In vitro studies to determine possible mechanisms of CpG immune-enhancing effects show that CpG ODN induce expression of costimulatory molecules on Ag-presenting cells and drive B cell isotype switching in the appropriate cytokine milieu. These studies demonstrate that CpG ODN are promising new immune enhancers for vaccination applications.